Variant rs759222737 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 5P and 2B. PM2PM5PP2BP4_Moderate

The NM_020693.4(DSCAML1):c.1231G>C(p.Val411Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,611,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V411I) has been classified as Pathogenic.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

DSCAML1
NM_020693.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.939

Variant links:

Genes affected

DSCAML1 (HGNC:14656): (DS cell adhesion molecule like 1) The protein encoded by this gene is a member of the Ig superfamily of cell adhesion molecules and is involved in neuronal differentiation. The encoded membrane-bound protein localizes to the cell surface, where it forms aggregates that repel neuronal processes of the same cell type. [provided by RefSeq, Sep 2016]

DSCAML1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr11-117518745-C-T is described in Lovd as [Pathogenic].

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), DSCAML1. . Gene score misZ 3.15 (greater than the threshold 3.09). Trascript score misZ 4.5764 (greater than threshold 3.09). GenCC has associacion of gene with motor neuron disorder, retinal disorder.

BP4

Computational evidence support a benign effect (MetaRNN=0.11725253).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSCAML1	NM_020693.4 linkuse as main transcript	c.1231G>C	p.Val411Leu	missense_variant	7/33	ENST00000651296.2	NP_065744.3	Q8TD84-1A0A384DVL8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DSCAML1	ENST00000651296.2 linkuse as main transcript	c.1231G>C	p.Val411Leu	missense_variant	7/33		NM_020693.4	ENSP00000498769.1	Q8TD84-1
DSCAML1	ENST00000321322.6 linkuse as main transcript	c.1411G>C	p.Val471Leu	missense_variant	7/33	1		ENSP00000315465.6	A0A384DVL8
DSCAML1	ENST00000651172.1 linkuse as main transcript	c.1411G>C	p.Val471Leu	missense_variant	7/33			ENSP00000498407.1	A0A384DVL8
DSCAML1	ENST00000527706.5 linkuse as main transcript	c.601G>C	p.Val201Leu	missense_variant	5/31	5		ENSP00000434335.1	Q8TD84-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000818

AC:

AN:

244382

Hom.:

AF XY:

0.0000151

AC XY:

AN XY:

132846

show subpopulations

Gnomad AFR exome

AF:

0.000127

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1459450

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726048

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.97

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.51

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.84

T;T

M_CAP

Benign

0.0056

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-1.0

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.41

N;N

REVEL

Benign

0.027

Sift

Benign

0.79

T;T

Sift4G

Benign

0.90

T;T

Vest4

0.28

MVP

0.39

MPC

0.55

ClinPred

0.11

GERP RS

1.1

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over